The project is aimed at: 1. elucidating the pathways of intracellular iron traffic and the molecular mechanisms involved in the regulation of intracellular iron metabolism, and 2. identifying and characterizing the molecular defect(s) underlying the expression of hereditary hemochromatosis. As a logical sequel to previous work in which the physiologic process by which iron is delivered to cells, the transferrin cycle, was characterized in K562 human erythroleukemia cells, a study was undertaken to gain insight into the intracellular distribution of iron between storage and utilization pools and to understand how this distribution is regulated. It was found, in K562 cells, that the fractional delivery of iron to ferritin (storage compartment) is strictly and directly correlated with the intracellular ferritin level. The relationship between ferritin levels and fractional delivery of iron to ferritin has been formulated as a nomogram, and has the characteristics of a partition. It is assumed, as a working hypothesis, that this partition serves to maintain cellular iron homeostasis with regard to iron utilization processes. It has further been found that, in K562 cells, the regulation of ferritin levels is highly dynamic in response to changes in iron supply to the cells, with respect to both biosynthesis and degradation. These findings are used to study whether cells from patients with hereditary hemochromatosis are different from normal cells with respect to the way they regulate their intracellular iron distribution.